This is an application for a Program Project to study the basic human neuroscience of cocaine action. We propose a coherent and highly integrated group of studies based on functional magnetic resonance imaging (fMRI) of human subjects and animal models. The basic scientific goals of the study are to (1) understand the circuitry in humans that underlies cocaine induced euphoria, withdrawal dysphoria and cocaine- conditioned craving, (2) to investigate differences in regional brain activation by cocaine in nondependent versus dependent users. In order to take full advantage of the strengths of fMRI, one aspect of the program involves technical development of this tool, optimizing its ability to image cortical and subcortical structures hypothesized to play key roles in the human brain reward circuitry. Animal models are used in the program because they are necessary to interpret the biological significance of human fMRI data and to relate it well validated molecular models of cocaine-induced neural activation.